Project Description

Alzheimer's disease (AD) is the most common cause of dementia, affecting one in nine individuals over the age of 65 with a total of 6.7 million Americans. It also ranks as the fifth-leading cause of death among individuals aged 65 and older, making it a significant public health crisis. Unfortunately, there is currently limited effective treatment available to prevent, halt, or reverse AD progression. Recent studies have highlighted the pivotal role of microglia, immune cells in the brain, in AD pathogenesis and their dysregulation in AD brains. Microglial cell therapy, which involves the transplantation of healthy microglia to replace dysfunctional microglia in AD patients, is a promising concept for AD treatment. However, significant knowledge gaps remain on optimal timing, method, and efficacy of delivering healthy human microglia to replace dysfunctional microglia in AD brains, as well as how to engineer microglia for maximum therapeutic impacts on AD pathology and cognitive functions. In this study, we will test these questions by transplanting engineered human pluripotent stem cells (hPSC)-derived human microglia into immunodeficient AD models that have AD pathologies and can receive human cells.

Start Date

03-2025

Postdoc Qualifications

The postdoc researchers who have a background in biomedical, biology, or engineering, and are interested in developing therapy for neurological disorders. 

Co-advisors

Chongli Yuan, cyuan@purdue.edu
Charles and Nancy Davidson Associate Professor of Chemical Engineering

Ranjie Xu, xu1726@purdue.edu
Department of Basic Medical Sciences, College of Veterinary Medicine

Bibliography

1. Ji, Y., McLean, J.L., and Xu, R*. (2024). Emerging Human PSC-based Human-Animal Brain Chimeras for Advancing Disease Modeling and Cell Therapy for Neurological Disorders. Neuroscience Bulletin 1-18.

2. Xu, R., X, Li., Boreland, A., Posyton, A., Kwan, K., Hart, R.P., and Jiang, P. (2020). Human iPSC-derived mature microglia retain their identity and functionally integrate in the chimeric mouse brain. Nature Communications 11 (1), 1-16 https://www.nature.com/articles/s41467-020-15411-9

3. Xu, R., Brawner, A., Li, S., Kim, H., Xue, H., Pang, Z., Kim, W.-Y., Hart, R., Liu, Y., and Jiang, P. (2019). OLIG2 drives abnormal neurodevelopmental phenotypes in human iPSC-based organoid and chimeric mouse models of Down syndrome. Cell Stem Cell 24 (6), 908-926. e8